Culture devices are known for example from the U.S. Pat. No. 5,501,971 which describes a culture vessel in which there is situated a culture zone external to an internal medium transfer conduit. The cells are situated in the external culture zone, which is a sort of basket comprising carriers, and the culture medium flows from top to bottom through this culture zone. Next the medium is recovered in the bottom part of the culture zone, it is taken up by means of a medium circulation device through the above mentioned conduit into a top part of the culture vessel and then passes again through the culture zone. The U.S. Pat. No. 5,507,971 describes several alternatives, but the medium always passes through the culture zone from top to bottom.
One drawback of such a device is that it is not adapted to all types of cell culture. Indeed this device is solely designed for cell culture on microcarriers in a fixed or close-packed bed, and is absolutely not suitable for cell culture in suspension or on microcarriers in a fluidised bed. Indeed, in the device of the U.S. Pat. No. 5,501,971, the cells in suspension without carriers or microcarriers or on non-immobilised carriers have a tendency to sediment and to accumulate in the bottom of the culture zone since they are subject to gravity and, as the flow of medium through this culture zone takes place from top to bottom, this accumulation of cells in the bottom of the culture zone is all the greater. Consequently the cells are packed on top of one another and are in contact with each other and the nutriments in this zone are not very accessible for the cells.
In the reactor of the U.S. Pat. No. 5,501,971, in the case of cultures, on non-immobilised carriers or microcarriers, of cells which are fragile species withstanding few stresses, the cells are subjected to the effect of gravity, to the descending flow of the medium and to the weight of the carriers, which enormously impairs the survival of the culture. In addition, an application for the culture in suspension is inconceivable in the bioreactor of the U.S. Pat. No. 5,501,971 since the cells in suspension can under no circumstances be subjected to cell to cell contact. Indeed, if such contacts are present, the cells create protein bonds between them and aggregate. Such aggregation creates cell death through lack of oxygen and nutriment.
U.S. Pat. No. 5,270,207, discloses a device wherein culture medium flows from the bottom to the top through the culture zone. The space inbetween the culture zone and the outer side wall of the device is filled with medium flowing upwards. The medium undergoes gas exchange in the upper space of the device whereafter it flows downwards again via a cylindrical zone in the center of the device towards the bottom of the device. In such devices, only a limited amount of gas exchange can take place, which makes these less suitable for cell culturing method wherein extensive cell growth or metabolism takes place.